Current methods for the synthetic manufacture of large fragments of DNA, a process commonly referred to as "gene synthesis," are expensive, labor- intensive and slow. We propose to develop a novel automated, solid-phase system for gene synthesis that will reduce costs and speed delivery times. Solid-phase synthesis has already been shown to work on a limited scale for constructing DNA fragments of approximately 300 bp in a non-automated fashion. We plan to apply a team of scientists with expertise in molecular biology, nucleic acid chemistry, software development, polymer chemistry and automation to the problem of developing and optimizing solid-phase gene synthesis. Our goal is a robust automation system that will rapidly and inexpensively produce gene-sized fragments of DNA (up to 10,000 bp in length). In Phase I we will focus on developing prototype procedures for solid-phase gene synthesis that are amenable to automation. We will also develop the computer software needed to design and order the oligonucleotides that will be used to assemble the desired fragment of DNA. In Phase II we will develop the instrumentation and software needed for the automation of gene synthesis. PROPOSED COMMERCIAL APPLICATIONS: The commercial applications for cost-effective synthesis of large DNA fragments are extensive. A major bottleneck in many biological research programs is the time-consuming process of cloning and modifying genes to prepare them for detailed analysis. Rapid access to custom-engineered genes could replace a substantial fraction of the total cloning effort in industrial research groups and academic laboratories.